Investigations will continue on hormonal relationships in normal and abnormal human pregnancy. The levels of a new estriol conjugate, estriol-3, 16-disulfate will be determined in peripheral blood, amniotic fluid and cord blood. Another new estrogen conjugate we discovered, the 15 alpha-N- acetylglucosaminide of 15 alpha-hydroxyestrone will be studied in a similar way after the development of the requisite methodology. An attempt will be made to develop a rapid method for the assay of estriol-16-glucosiduronate and estriol-3-sulfate-16- glucosiduronate to see whether the ratio is abnormal in diseases of pregnancy such as diabetes, placental insufficiency etc. as it is in Rh- isoimmunization. In non pregnancy we intend to assay for plasma estriol in women, preparatory to a study on the possible relationship between estriol and breast cancer. The final area concerns uterine proteases and their possible connection with fertility and cancer. Studies will involve the analysis of human endometrium not needed by the pathologist and the analysis of rodent uteri. We will assay for trypsin-like proteolytic activity and study acrylamide gel electrophoretic profiles of histones. In the human we will see whether these parameters vary with the menstrual cycle. In the rodent the influence of specific protease inhibitors on the estrus cycle and reproduction will be examined.